Platelets prevent hemorrhage by a secretory process which is stimulated by an intracellular chain of biochemical events similar to that in all other secretory cells. Although tyrosine kinases (TKs), which control placement of phosphates on tyrosine residues of protein, are associated with major biological effects such as cell growth, receptor activity, and oncogene mutation, biochemical mechanisms underlying these events are only partially known. We found that high levels of cytoplasmic Ca++ promotes tyrosine phosphorylation, particularly of a 130 kD cytoplasmic activates tyrosine dephosphorylation of the same protein. Finding that levels of cytoplasmic and stored Ca++ affect tyrosine phosphorylation by controlling phosphatase activity is the first recognition of a specific physiologic role for a tyrosine phosphatase (TP). Because reciprocal interaction between a TK and a TP appears to control Ca++ flux and phosphorylation of the 130 kDa protein, this protein may be involved in Ca++ channel function. Other significant cellular events such as cell growth, cell-to-cell interaction, contact inhibition, and malignant transformation may depend on relationships we have defined between TKs, TPs, Ca++ distribution, Ca++ flux, and secretion. Linkage between the coagulation process and inflammation is suggested by vascular damage and intravascular clotting that occurs in septic shock and by infiltration of inflammatory cells in areas of vascular damage due to atherosclerosis. Activation of platelets by clotting factors is well characterized but whether clotting factors can activate monocytes and leukocytes is not known. We found that reaction between thrombin and a thrombin receptor on cultured monocytes causes generation of prostaglandins, leukotrienes, and HETEs, which are products of monocyte activation. This response is mediated by the thrombin site that binds hirudin. These findings indicate that release of monocyte interleukins and tissue necrosis factor may be the link between coagulation, inflammation, and the vascular damage evident in septic shock and atherosclerosis.